An Open Label Study of Multiple Doses of Cannabidiol in the Prevention of Acute Graft-Versus-Host Disease (GVHD)
- Registration Number
- NCT03840512
- Lead Sponsor
- Kalytera Therapeutics Israel, Ltd.
- Brief Summary
A prospective, open-label, phase 2a study, to evaluate the pharmacokinetic (PK) profile, safety, and efficacy of multiple doses of Cannabidiol (CBD) in participants Graft-Versus-Host Disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT)
- Detailed Description
The study contains 3 cohorts of 12 participants each: All participants will be orally administered for 105 days with CBD at doses of 75, 150 or 300 mg (PO) BID for the prevention of acute GVHD (aGVHD) following allogeneic HSCT.
In addition to the study drug, all participants will receive standard aGVHD prophylaxis consisting of a calcineurin inhibitor (cyclosporine or tacrolimus) and a short course of methotrexate (MTX). After completion of 105 treatment days, the participant will be followed-up until day 180.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 36
- Any malignant hematological disease in CR or Myelodysplastic Syndrome (MDS)
- Age ≥ 18 years
- Karnofsky Score (KS) ≥ 60%
- HSCT-Comorbidity Index (HSCT-CI) score ≤ 3
- No major organ dysfunction
- Myeloablative or reduced intensity conditioning regimen
- Matched (7/8 or 8/8) unrelated donor
- Peripheral blood stem cell graft
- Female subjects of childbearing potential must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for the follow-up time period. Acceptable methods of contraception include abstinence, barrier method with spermicide, intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method.
- Male subjects with partners of childbearing potential must agree to use adequate contraception (barrier method or abstinence) during the study.
- Subject's written informed consent
- Malignant hematological disease other than MDS, not in CR
- Myelofibrosis
- Allogeneic transplantation from a matched or mismatched sibling donor
- Cord blood transplantation
- Positive serology for HIV
- Serious psychiatric or psychological disorders
- Any uncontrolled infection at time of registration
- Active consumption of illicit drugs (such as: Crack cocaine, Heroin, Methamphetamines, Cocaine, Bath Salts, Amphetamines, Methadone, Benzodiazepine, Ecstasy)
- Use of Cannabis and/or its derivatives fourteen days prior to HSCT and for the duration of study participation
- Uncontrolled hepatitis B or active hepatitis C infection.
- QTc>450ms per Fridericia's correction and Impaired cardiac function or clinically significant cardiac diseases
- Inadequate renal function defined as measured creatinine clearance > 2.0 mg/dl
- Liver enzymes: ALT and AST > 3x upper limit of normal
- Pregnancy or breastfeeding ((positive serum β-HCG 7 days before first dose)
- Treatment with another investigational drug, biological agent, or device within 30 days of first dose, or investigational cell therapy within 6 months of first dose
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Oral CBD 150 BID CBD - Oral CBD 75 BID CBD - Oral CBD 300 BID CBD -
- Primary Outcome Measures
Name Time Method Adverse Events (AEs) and serious adverse events (SAEs) Reporting Up to day 180 All AEs will be recorded, whether considered minor or serious, drug-related or not
Cumulative incidence of aGVHD at day 100 post-transplant First 100 days after transplant Cumulative Incidence of Grade B-D aGvHD
Pharmacokinetic parameters of Cannabidiol (CBD) - Tlag Blood samples will be obtained on Day 7 before HSCT and Day 7 post HSCT. Sampling times: immediately after CBD dosing and at 15, 30, 45, 60, 120, 180, and 240 minutes, and 8, 12 and 24 hours after dosing of CBD Pharmacokinetic (PK) profile - Tlag - Absorption lag-time defined as the time of the first concentration ≥ Limit of Quantitation (LOQ)
Pharmacokinetic parameters of Cannabidiol (CBD) - Cmax Blood samples will be obtained on Day 7 before HSCT and Day 7 post HSCT. Sampling times: immediately after CBD dosing and at 15, 30, 45, 60, 120, 180, and 240 minutes, and 8, 12 and 24 hours after dosing of CBD Pharmacokinetic (PK) profile - Cmax - Maximum Plasma Concentration
Pharmacokinetic parameters of Cannabidiol (CBD) - Tmax Blood samples will be obtained on Day 7 before HSCT and Day 7 post HSCT. Sampling times: immediately after CBD dosing and at 15, 30, 45, 60, 120, 180, and 240 minutes, and 8, 12 and 24 hours after dosing of CBD Pharmacokinetic (PK) profile - Tmax - time to reach maximum plasma concentration
Pharmacokinetic parameters of Cannabidiol (CBD) - AUC0-t Blood samples will be obtained on Day 7 before HSCT and Day 7 post HSCT. Sampling times: immediately after CBD dosing and at 15, 30, 45, 60, 120, 180, and 240 minutes, and 8, 12 and 24 hours after dosing of CBD Pharmacokinetic (PK) profile - AUC0-t - area under the plasma concentration-time curve (AUC0-t) up to the last quantifiable concentration (LOQ) from time of administration (t=0) up to the selected
Pharmacokinetic parameters of Cannabidiol (CBD) - λz Blood samples will be obtained on Day 7 before HSCT and Day 7 post HSCT. Sampling times: immediately after CBD dosing and at 15, 30, 45, 60, 120, 180, and 240 minutes, and 8, 12 and 24 hours after dosing of CBD Pharmacokinetic (PK) profile: λz - Elimination rate constant determined by linear regression of the terminal points of the ln-linear plasma concentration-time curve
Pharmacokinetic parameters of Cannabidiol (CBD) - T1/2 Blood samples will be obtained on Day 7 before HSCT and Day 7 post HSCT. Sampling times: immediately after CBD dosing and at 15, 30, 45, 60, 120, 180, and 240 minutes, and 8, 12 and 24 hours after dosing of CBD Pharmacokinetic (PK) profile: T1/2 - Terminal elimination half-life
Pharmacokinetic parameters of Cannabidiol (CBD) - AUC0-∞ Blood samples will be obtained on Day 7 before HSCT and Day 7 post HSCT. Sampling times: immediately after CBD dosing and at 15, 30, 45, 60, 120, 180, and 240 minutes, and 8, 12 and 24 hours after dosing of CBD Pharmacokinetic (PK) profile: AUC0-∞ - area under the plasma concentration-time curve extrapolated to infinity
Cumulative incidence of aGVHD at day 180 post-transplant Day 180 post-transplant Cumulative Incidence of Grade 2-4 aGvHD
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (5)
St Vincent's Hospital Sydney - The Kinghorn Cancer Centre
🇦🇺Sydney, Australia
Davidof Cancer Center, Beilinson hospital, Rabin medical center
🇮🇱Petach Tikva, Israel
Hadassah Medical Center - Bone Marrow Transplantation Department, Cancer Immunotherapy and Immunobiology Research Center
🇮🇱Jerusalem, Israel
Rambam Health Care - Bone Marrow Transplantation Unit
🇮🇱Haifa, Israel
Tel-Aviv Sourasky Medical Center - Bone Marrow Transplantation Unit
🇮🇱Tel Aviv, Israel